Network inference and community detection, based on covariance matrices, correlations and test statistics from arbitrary distributions

In this paper we propose methodology for inference of binary-valued adjacency matrices from various measures of the strength of association between pairs of network nodes, or more generally pairs of variables. This strength of association can be quantified by sample covariance and correlation matrices, and more generally by test-statistics and hypothesis test p-values from arbitrary distributions. Community detection methods such as block modelling typically require binary-valued adjacency matrices as a starting point. Hence, a main motivation for the methodology we propose is to obtain binary-valued adjacency matrices from such pairwise measures of strength of association between variables. The proposed methodology is applicable to large high-dimensional data-sets and is based on computationally efficient algorithms. We illustrate its utility in a range of contexts and data-sets

Detection of Epigenomic Network Community Oncomarkers

In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as DNA methylation reflect environmental risk factors, and are increasingly recognised for their fundamental role in diseases such as cancer. DNA methylation is a gene-regulatory pattern, and hence provides a means by which to assess genomic regulatory interactions. Network models are a natural way to represent and analyse groups of such interactions. The utility of network models also increases as the quantity of data and number of variables increase, making them increasingly relevant to large-scale genomic studies. We propose methodology to infer prognostic genomic networks from a DNA methylation-based measure of genomic interaction and association. We then show how to identify prognostic biomarkers from such networks, which we term `network community oncomarkers'. We illustrate the power of our proposed methodology in the context of a large publicly available breast cancer dataset

Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging

Small interfering RNA (siRNA) molecules are potent effectors of post-transcriptional gene silencing. Using noninvasive bioluminescent imaging and a mathematical model of siRNA delivery and function, the effects of target-specific and treatment-specific parameters on siRNA-mediated gene silencing are monitored in cells stably expressing the firefly luciferase protein. In vitro, luciferase protein levels recover to pre-treatment values within <1 week in rapidly dividing cell lines, but take longer than 3 weeks to return to steady-state levels in nondividing fibroblasts. Similar results are observed in vivo, with knockdown lasting ~10 days in subcutaneous tumors in A/J mice and 3–4 weeks in the nondividing hepatocytes of BALB/c mice. These data indicate that dilution due to cell division, and not intracellular siRNA half-life, governs the duration of gene silencing under these conditions. To demonstrate the practical use of the model in treatment design, model calculations are used to predict the dosing schedule required to maintain persistent silencing of target proteins with different half-lives in rapidly dividing or nondividing cells. The approach of bioluminescent imaging combined with mathematical modeling provides useful insights into siRNA function and may help expedite the translation of siRNA into clinically relevant therapeutics for disease treatment and management

Study of growth parameters for refractory carbide single crystals Quarterly status report no. 7, Sep. 1 - Dec. 1, 1965

Crystal growth experiments to explore influence of atmospheric compositions, during melting, on crystal stochiometry emphasizing determination of tantalum solubilit

Active control of spacecraft charging on ATS-5 and ATS-6

Effects on spacecraft ground potential of active emission of charged particles are being investigated through experiments using the ATS-5 and ATS-6 spacecraft. Each spacecraft is equipped with ion engine neutralizers which emit low energy charged particles. Despite great differences in design between the two spacecraft, they attain similar potentials in similar environments. Therefore, effects on spacecraft potential of neutralizer operations can be used to compare the effects of operating the two different neutralizers (hot wire filament and plasma bridge). The neutralizers on both spacecraft were operated in eclipse. Results of these operations are presented and spacecraft responses compared

A low-power asynchronous VLSI FIR filter

An asynchronous FIR filter, based on a Single Bit-Plane architecture with a data-dependent, dynamic-logic implementation, is presented. Its energy consumption and sample computation delay are shown to correlate approximately linearly with the total number of ones in its coeflcient-set. The proposed architecture has the property that coefficients in a Sign-Magnitude representation can be handled at negligible overhead which, for typical filter coefficient-sets, is shown to offer significant benefits to both energy consumption and throughput. Transistor level simulations show energy consumption to be lower than in previously reported designs

Can lay-led walking programmes increase physical activity in middle aged adults? : a randomised controlled trial

Study objective: To compare health walks, a community based lay-led walking scheme versus advice only on physical activity and cardiovascular health status in middle aged adults. Design: Randomised controlled trial with one year follow up. Physical activity was measured by questionnaire. Other measures included attitudes to exercise, body mass index, cholesterol, aerobic capacity, and blood pressure. Setting: Primary care and community. Participants: 260 men and women aged 40–70 years, taking less than 120 minutes of moderate intensity activity per week. Main results: Seventy three per cent of people completed the trial. Of these, the proportion increasing their activity above 120 minutes of moderate intensity activity per week was 22.6% in the advice only and 35.7% in the health walks group at 12 months (between group difference =13% (95% CI 0.003% to 25.9%) p=0.05). Intention to treat analysis, using the last known value for missing cases, demonstrated smaller differences between the groups (between group difference =6% (95% CI -5% to 16.4%)) with the trend in favour of health walks. There were improvements in the total time spent and number of occasions of moderate intensity activity, and aerobic capacity, but no statistically significant differences between the groups. Other cardiovascular risk factors remained unchanged. Conclusions: There were no significant between group differences in self reported physical activity at 12 month follow up when the analysis was by intention to treat. In people who completed the trial, health walks was more effective than giving advice only in increasing moderate intensity activity above 120 minutes per week

Study of growth parameters for refractory carbide single crystals Quarterly status report no. 6, 1 Jun. - 1 Sep. 1965

Growth parameters for refractory tantalum carbide single crystal